Partial contribution of polyamines to the relaxant effect of 17 alpha-estradiol in rat uterine smooth muscle.
1. The effects of 17 alpha-estradiol on KCl (60 mM), CaCl2 (30 microM to 10 mM) and vanadate (0.3 mM)-induced contractions in rat uterus have been assayed. Furthermore, the effect of 17 alpha-estradiol on calmodulin-stimulated cAMP-phosphodiesterase activity was also studied. 2. 17 alpha-estradiol relaxed the tonic contraction induced by KCl (60 mM) in a concentration-dependent way (IC50, 8.3 +/- 0.7 microM), and CaCl2 (0.1 to 10 mM) counteracted it. 3. CaCl2 (30 microM to 10 mM) produced concentration-dependent contraction of rat uterus in a calcium-free medium supplemented with 60 mM of KCl (EC50: 0.2 +/- 0.01 mM). 17 alpha-estradiol (8 microM) antagonized the contraction induced by CaCl2, increasing the EC50 value up to 0.7 +/- 0.1 mM (P < 0.01). 4. 17 alpha-estradiol (0.1 to 1 mM) relaxed in a concentration-dependent way the tonic contraction induced by vanadate in rat uterus incubated in a calcium-free medium and EDTA supplemented. The maximal relaxation achieved with 1 mM of 17 alpha-estradiol was 52.2 +/- 2.8%. 5. 17 alpha-estradiol (1 to 100 microM) did not modify the basal activity of cAMP-phosphodiesterase but inhibited the calcium plus calmodulin stimulated activity. The maximal inhibition achieved was 43 +/- 5.4%. 6. The relaxing effect of 17 alpha-estradiol on KCl (60 mM)-induced tonic contraction was unmodified with the antioestrogen tamoxifen (0.1 and 1 microM), the inhibitor of tirosine kinase (genistein, 10 microM) and the cAMP-dependent protein kinase inhibitor (Rp-adenosine 3',5'-monophosphothioate, triethylamine salt, 100 microM). However, the effect was antagonized with the inhibitor of transcription (actinomycin D, 5 micrograms/ml,), the inhibitor of protein synthesis (cycloheximide, 10 and 100 micrograms/ml), and the inhibitor of ornithine decarboxilase (alpha-difluoromethyl-ornithine, 10 mM). 7. Our results suggest that polyamines contribute to the relaxant effect of 17 alpha-estradiol in rat uterine smooth muscle behaving, presumably, as mediators of the transcriptional component involved in the effect of 17 alpha-estradiol.
Gutiérrez
M
M
Departamento de Medicina, Facultad de Medicina, Universidad de Oviedo, Spain.
Fernández
A I
AI
Revuelta
M P
MP
Cantabrana
B
B
Hidalgo
A
A
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000502:physiology*; D002122:Calcium Chloride / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009126:Muscle Relaxation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology
D015317:Biogenic Polyamines; D002147:Calmodulin; D014638:Vanadates; D004958:Estradiol; D011189:Potassium Chloride; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D002122:Calcium Chloride